Indoxyl Sulfate Predicts Cardiovascular Disease and Renal Function Deterioration in Advanced Chronic Kidney Disease

Abstract

Indoxyl sulfate, a protein-bound uremic toxin, was found to be accumulated in kidney tissues with a reduction in renal function. This, in turn, not only leads to kidney fibrosis and endothelial dysfunction but also to adverse clinical effects. We investigated the adverse effects of indoxyl sulfate on clinical outcomes in a study involving human subjects. Seventy pre-dialysis patients were enrolled from a single medical center. Serum indoxyl sulfate and biochemistry data were measured concurrently. Clinical outcomes including dialysis event, cardiovascular event and all-cause mortality were recorded during a 36-month follow-up. Multivariate Cox regression analysis showed that age (HR: 0.95, p=0.05), serum creatinine (HR: 1.29, p=0.04) and indoxyl sulfate (HR: 1.06, p=0.02) were independently associated with dialysis event; age (HR: 1.16, p=0.01), serum phosphate (HR: 3.03, p=0.05) and indoxyl sulfate level (HR: 1.11, p=0.04) reached significant correlation with cardiovascular events after adjusting for other confounding factors. Kaplan-Meier analysis revealed that indoxyl sulfate level was significantly associated with cardiovascular and dialysis event (log rank p <0.01, log rank p=0.01, respectively). In addition, serum indoxyl sulfate concentration was significantly increased in patients with dialysis and cardiovascular event (p <0.01, p <0.01, respectively). Our results suggest that serum indoxyl sulfate level was a valuable marker in predicting cardiovascular disease and renal function decline in patients with advanced chronic kidney disease.